关键词： Inflammatory bowel disease   Crohn's disease   Ulcerative colitis   Small molecules   Natural products  

摘要： Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease in the gastrointestinal tract emerged as a public health challenge worldwide. IBD exhibits a relapsing and remitting course results in negative impacts on both physical and psychological health of IBD patients. Great efforts have been made during the past few years, but relatively limited drugs are currently available for the management of IBD. Clinically, there is a strong demand for new drugs for the treatment of IBD with better efficacy and lower side effects. This review focuses on the drug discovery process of the anti-IBD agents, aiming to introduce the general characteristics of 180, as well as systematically summarize the recent advances in the discovery of small-molecule candidates and natural products with promising in vivo potential for the treatment of IBD. (C) 2019 Elsevier Masson SAS. All rights reserved.

关键词： Anemia   Crohn's disease   Disease activity   Fatigue   Inflammatory bowel disease   Ulcerative colitis  

摘要： Fatigue is a burdensome, multidimensional, and multifactorial symptom that is associated with a wide array of chronic illnesses, specifically occurring in nearly 50% of patients with inflammatory bowel disease (IBD). Although common, given its subjective nature, physicians often under-recognize and undertreat this debilitating symptom. There are multiple etiologies that can contribute to fatigue in patients with IBD, including disease activity, anemia, medications, psychosomatic symptoms, and alterations to the gut-brain axis. The management of fatigue in IBD can be challenging, as it is often times multifaceted. In this review, we summarize the available tools for the diagnosis and measurement of fatigue, discuss etiologies, and make recommendations for their management. We identify knowledge gaps for the workup and treatment of fatigue and propose an algorithm to aid physicians in the evaluation and management of fatigue in this unique population. However, future research is needed to address several areas of knowledge deficits and improve the management of fatigue in IBD.

摘要： The percentage of our patients, as a proportion of IBD patients sequenced, possessing these alleles is 1.2% (5 patients), contrasting to the 1 patient (0.22-0.35%) expected from curated frequency databases. Three patients (patients 1, 3, and 4) harbored the common synonymous p.E232E variant (CADD 9.5) and one (patient 5) harbored the synonymous p.S66S variant (CADD 17.63). In this study, we identify five pediatric IBD patients harboring variants on the same chromosome, previously described as disease-causing when inherited in compound heterozygosity. [Extracted from the article]

关键词： internal consistency   item construct   participant response patterns   readability   validity  

摘要： Aim Paediatric inflammatory bowel disease (IBD) is a chronic relapsing condition requiring adherence to complex treatment regimens to achieve best outcomes. Adherence is frequently low in this population but can be improved by increasing disease- and treatment-related knowledge. The IBD-knowledge inventory device (IBD-KID) is a knowledge assessment tool specifically developed and validated for children with IBD. To analyse IBD-KID participant response patterns in order to review the strength of the tool. Methods A cohort of children with IBD completed IBD-KID, and their responses were used to assess the tool's validity and feasibility. Item response analysis assessed the item difficulty and the ability of items to discriminate between high/low scorers. The analysis considered item structure, readability and the effectiveness of multiple choice items. Results A total of 105 completed IBD-KID assessments showed that 12 items (52%) had an acceptable difficulty level, and 17 (74%) were effective at discriminating between high/low scorers. Nine (61%) had good readability, but comprehension levels ranged from 5 to 18 years. Seven (30%) had elevated 'don't know' responses, highlighting the need for content and construction review. Of the 10 multiple choice items, 9 were complex and not functioning efficiently. Internal consistency was acceptable but could be improved by removing two items. Conclusions The response analysis metrics were reviewed by an expert panel and provided a framework for IBD-KID improvements with the aim of increasing discrimination and reducing difficulty without adversely affecting reliability. The proposed revisions will address components that may have caused children to answer incorrectly due to confusion rather than lack of knowledge.

关键词： Crohn's disease (CD)   Inflammatory bowel disease (IBD)   Mannose-binding lectin (MBL)   MBL2 gene   Ulcerative colitis (UC)  

摘要： Inflammatory bowel disease (IBD) refers to disorders associated with progressive inflammatory processes in the gastrointestinal system. IBD consists of two major forms, Crohn's disease (CD), and ulcerative colitis (UC). IBD became a global disease in the 21st century. Its pathogenesis is still not fully understood. Mannose-binding lectin (MBL) is a pattern-recognising molecule, involved in anti-microbial and anti-cancer immunity. It is able to opsonize microorganisms and abnormal host cells, and to initiate complement activation. The aim of this study was to investigate possible involvement of MBL in inflammatory bowel disease in adults. Forty persons diagnosed with CD and 28 with ulcerative colitis were recruited. The control group consisted of 136 healthy persons. Single nucleotide polymorphisms of the MBL2 gene (localised to both promoter and exon 1) were determined as were serum MBL concentrations. The exon 1 variant alleles and MBL deficiency-associated genotypes were more frequent among patients compared with controls, although this difference was not statistically significant. No differences of MBL levels were found between the major groups. However in MBL2 A/A homozygous IBD patients, the median was significantly higher than in corresponding healthy subjects. That was particularly evident in the case of active Crohn's disease (1493 ng/ml vs. 800 ng/ml, p = 0.021). It may suggest that MBL and MBL-dependent complement activation contributes to excessive inflammation and its adverse effects in the course of CD. It cannot also be excluded that high MBL activity constitutes in some cases part of a multifactorial network conducing to development of CD.

关键词： Mesalamine   Prednisolone   Immunomodulators   Biologics   Janus kinase inhibitors  

摘要： The current goal of inflammatory bowel disease (IBD) treatment is a symptom-free everyday life accompanied by mucosal healing with minimal use of corticosteroids. Recent therapeutic advances, particularly, the emergence of anti-tumor necrosis factor (anti-TNF) antibodies, have changed the natural history of IBD. Additionally, these advances also led to the emergence of the therapeutic concept of the "treat to target" strategy. With the development of new drugs and clinical trials, not only biologics but also small molecules have been applied to clinical practice to better individualize and optimize therapy. However, if newer drugs, including anti-TNF therapies, are recommended for all patients diagnosed with IBD, a significant number of patients will be overtreated. The basic goal of IBD treatment is still to make the best use of conventional treatments based on IBD pathophysiology. Thus, physicians should be familiar with the modes of action of the available drugs. In this review, the author discusses the existing data for many approved drugs and provide insights for optimizing current treatments for the management of patients with IBD in the era of biologics.

关键词： anti-integrin therapy   Crohn's disease   ulcerative colitis   inflammatory bowel disease   integrins  

摘要： Inflammatory bowel disease (IBD) is characterized by uncontrolled inflammation in the gastrointestinal tract. The underlying pathobiology of IBD includes an increase in infiltrating gut-homing lymphocytes. Although lymphocyte homing is typically a tightly regulated and stepwise process involving multiple integrins and adhesion molecules expressed on endothelial cells, the distinct roles of integrin-expressing immune cells is not fully understood in the pathology of IBD. In this review, we detail the involvement of integrins expressed on specific lymphocyte subsets in the pathogenesis of IBD and discuss the current status of approved and investigational integrin-targeted therapies.

关键词： adalimumab   infliximab   quality improvement  

摘要： Objectives: Adequate serum drug levels of tumor necrosis factor-alpha inhibitors (anti-TNF) have been shown to improve outcomes in patients with inflammatory bowel disease. We aim to describe the quality improvement (QI) methods used at our institution to improve post-induction therapeutic drug monitoring (TDM) in children initiating anti-TNF therapy (infliximab and adalimumab) and describe the frequency of subtherapeutic anti-TNF levels. Methods: Beginning in February 2016, all patients initiating anti-TNF therapy were identified and tracked. Interventions to improve TDM, including the initiation of therapy plans for infliximab, real-time reminders for practitioners, and scheduling modifications for those initiating anti-TNF therapies were implemented using the Institute for Healthcare Improvement Plan-Do-Study-Act cycle approach. Statistical process control charts were used to demonstrate improvement over time. Anti-TNF levels and presence of antidrug antibodies were also recorded. Results: Using QI methodology, we improved post-induction anti-TNF TDM from a baseline of 43% in 2015 to >80% by the end of 2017, with sustained improvement. Infliximab post-induction TDM improved from a baseline of 59% to 82%, whereas adalimumab post-induction TDM improved from baseline of 14% to 79%. In total, 36% of all anti-TNF post-induction levels were <5 mu g/mL, with nearly 60% of post-induction infliximab levels being Conclusions: Through incremental QI approaches, we improved the utilization of anti-TNF post-induction TDM with sustained improvement, approaching our goal of 90%. Subtherapeutic post-induction infliximab levels were common, indicating a strong need for anti-TNF TDM and an opportunity for dose optimization.

摘要： Background Inflammatory bowel disease (IBD) is a significant health problem in the industrialised world, currently increasing in developing countries. Understanding the global burden of IBD is important to tackle increasing disease occurrence. Aim To investigate the GBD (Global Burden of Disease) 2017 Study Database summarising and critically evaluating the global burden of IBD Methods We presented age-standardised prevalence estimates, disability-adjusted life years (DALYs) and its components: years lived with disability (YLDs) and years of life lost (YLLs) due to premature mortality. We reported these measures from 1990 to 2017 and stratified by region, socio-demographic index (SDI), gender and age group. Results The latest IBD prevalence and burden estimates varied widely across regions, and were particularly elevated in high-SDI countries. Despite an increasing prevalence from 1990 to 2017 (+6%), the IBD burden decreased (DALYs -12%). This decrease was driven by IBD-associated premature mortality (YLLs -26%). This measure represented a high share of disease burden in low-SDI countries (86% of DALYs), whereas disability constituted the predominant component in high-SDI countries (71%) in 2017. Disease burden decreased particularly in children (DALYs -39% and YLLs -52%). In the last 10 years, however, prevalence plateaued in middle- to high-SDI countries and steeply increased in low-SDI countries. Conclusions These findings highlight significant improvements in IBD care in the last three decades, particularly in children. The global burden of IBD and premature mortality have progressively decreased. The increase in disease frequency observed in developing countries is worrying, especially considering the high associated premature mortality in these areas.